As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

OBJECTIVE To investigate the efficacy and safety of tirofiban for early neurological deterioration in patients with acute ischemic stroke. METHODS A total of 126 patients with early neurological deterioration of acute ischemic stroke who were admitted to the Department of Neurology， Heji Hospital Affiliated to Changzhi Medical College from January 2022 to December 2023 were selected and divided into observation group and control group according to random number table method， with 63 cases in each group. All patients received standardized treatment such as lipid-lowering and blood pressure-lowering therapy. Based on the standard treatment， patients in the control group additionally took Aspirin enteric-coated tablets 100 mg+Clopidogrel bisulfate tablets 75 mg orally （once a day， for 14 consecutive days）. The patients in the observation group received Tirofiban hydrochloride and sodium chloride injection based on the standardized treatment [first intravenous infusion of 0.40 μg/（kg·min） for 30 min， and then continuous intravenous infusion of 0.10 μg/（kg·min） for 47.5 h]； subsequently， patients were given Aspirin enteric-coated tablets （100 mg） and Clopidogrel bisulfate tablets （75 mg） once a day for 14 consecutive days. The clinical efficacy， the National Institutes of Health Stroke Scale （NIHSS） score， modified Rankin Scale （mRS） score， and hemorheological indexes before and after treatment were compared between the two groups， and the adverse reactions were recorded. RESULTS The total effective rate （87.30%） of the observation group was significantly higher than that of the control group （71.43%） （P＜0.05）. NIHSS scores of the two groups at 1st， 7th and 14th day after treatment， the mRS score at 90th day after treatment， and the platelet aggregation rate， whole blood viscosity， plasma viscosity and fibrinogen at 14th day after treatment were significantly lower than those before treatment in the same group， and the observation group was significantly lower than the control group at the same period （P＜0.05）. The total incidences of adverse reactions such as nausea， headache， fever， gastrointestinal bleeding， oral and nasal mucosal bleeding and thrombocytopenia in both groups of patients were 28.57% respectively， with no statistically significant difference （P＞0.05）. CONCLUSIONS For patients with early neurological deterioration in acute ischemic stroke， the addition of tirofiban can accelerate the recovery of neurological function， improve blood hyperviscosity and platelet aggregation， and improve the prognosis of patients with good safety.

Objective:To evaluate the clinical efficacy of returning, squeezing, patting and pulling orthopaedic manipulation combined with pelvic fabric tape fixation for the treatment of postpartum pubic symphysis separation.Methods:The clinical data of 80 patients with postpartum pubic symphysis separation from June 2015 to March 2019 were retrospectively analyzed, and all of them were given orthopaedic manipulative therapy using return squeezing and patting and pulling, once a week, for a total of 3 times. After the manipulative treatment, the patients were instructed to brake the pelvic fixation straps for not less than 8 h per day, and digital X-ray (DR) pelvic radiographs or ultrasound tests were performed before and after the treatment to measure the distance between the pubic symphysis. VAS scale was used to assess the degree of pain, and the Oswestry dysfunction index (ODI) was used to assess the degree of dysfunction. The clinical efficacy was evaluated.Results:After treatment of 80 patients, 6 showed significant improvement, 69 showed improvement, and 5 showed no improvement, with a total effective rate of 93.8%. Compared with before group, the inter-pubic symphysis distance [(15.09±3.10) mm, (12.01±4.36) mm, (9.64±0.30) mm, (8.18±1.56) mm vs. (19.35±1.08) mm, F=254.64] were significantly smaller at 1 week, 2 weeks, 3 weeks, and 1 month ( P<0.001); VAS scores (2.90±1.24, 1.29±0.88, 0.84±0.43, 0.56±0.32 vs. 6.11±2.93, F=122.60) were significantly lower than before treatment ( P<0.001); ODI (28.09±4.30, 22.01±4.95, 20.64±0.41, 14.18±1.36 vs. 45.43±4.01, F=734.17) were significantly reduced ( P<0.001). Conclusion:Returning, squeezing, patting and pulling orthopaedic manipulation combined with pelvic fabric tape fixation can quickly restore the separation distance of the pubic symphysis, reduce local pain and improve lumbosacral function.

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Gastrointestinal tumors （GTs）， including colorectal cancer， gastric cancer， liver cancer， pancreatic cancer， and esophageal cancer， are increasing in incidence worldwide and have become one of the major diseases threatening human health. Tumor stem cells （TSCs）， an undifferentiated subpopulation within tumor tissues， possess biological characteristics such as self-renewal， multidirectional differentiation， high tumorigenicity， and resistance to radiochemotherapy. They play an important role in the occurrence， progression， recurrence， and metastasis of GTs and have increasingly become a research hotspot in GT treatment. Although modern medicine has made remarkable progress， there remain many problems in therapeutic approaches targeting TSCs. In this context， traditional Chinese medicine （TCM）， with its favorable safety profile and multi-target mechanisms， has shown potential advantages and value in regulating TSCs. It can reduce TSC drug resistance， enhance the sensitivity of tumor cells to chemotherapeutic agents， inhibit tumor growth and metastasis， and has shown unique advantages in improving the quality of life and prolonging the survival of GT patients. Studies have found that active components of Chinese medicine， such as terpenoids， polyphenols， flavonoids， glycosides， and quinones， and Chinese medicine compound formulas， including Zuojin pills， Sijunzi decoction， Biejiajian pills， and Xuanfu Daizhe decoction， can inhibit TSCs-related signaling pathways such as the Notch signaling pathway， the Wnt/β-catenin signaling pathway， the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， and the Hippo signaling pathway. They also reduce the expression of TSC surface markers， including sex-determining region Y-box 2 （SOX2）， sex-determining region Y-box 9 （SOX9）， octamer-binding transcription factor 4 （OCT4）， prominin-1 （CD133）， cluster of differentiation 44 （CD44）， cluster of differentiation 24 （CD24）， and thyroid transmembrane protein 1 （CD90）， thereby hindering TSC differentiation， accelerating their metabolic processes， improving the tumor microenvironment， and consequently inhibiting GT growth. This study collects and analyzes recent research on the regulation of TSCs by TCM in the treatment of GT， aiming to provide a new theoretical basis for tumor therapy with TCM， expand its application in the comprehensive treatment of GT， and offer new therapeutic ideas and methods for clinical practice.

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective To identify the risk factors for newly developed lower extremity deep vein thrombosis(DVT)in patients transferred to the anesthesia intensive care unit(AICU)after general anes-thesia.Methods A total of 192 patients who were transferred to AICU with tracheal intubation after elective general anesthesia from May 2022 to August 2022,105 males and 87 females,aged 18-85 years,BMI 18-31 kg/m2,ASA physical status Ⅱor Ⅲ,were retrospectively collected.The patients'baseline da-ta,anesthesia surgery data and preoperative and postoperative laboratory examination data were obtained.The patients were divided into two groups according to the results of ultrasound within 6 hours after admission to the AICU:DVT group and non-DVT group.Multivariate logistic regression analysis was used to analyze the risk factors and 95%confidence interval(CI)of DVT in AICU patients within 6 hours after sur-gery.ResultsNew DVT occurred in 64 patients(33.3%)in AICU after general anesthesia were calf inter-muscular venous thrombosis(CMVT).Multivariate logistic regression analysis showed that preoperative ar-rhythmia(OR = 2.236,95%CI 1.011-4.943,P = 0.047),high preoperative platelet count(OR = 1.006,95%CI 1.002-1.010,P = 0.007),high preoperative D-dimer concentration(OR=1.203,95%CI 1.046-1.383,P = 0.010),intraoperative hypotension(OR = 1.010,95%CI 1.002-1.019,P = 0.020),and intraoperative norepinephrine application(OR = 3.796,95%CI 1.697-8.492,P = 0.001)were risk factors for new DVT formation in AICU patients after general anesthesia.History of regular intake of aspirin(OR = 0.176,95%CI 0.060-0.518,P = 0.002)was protective factor.Conclusion Preoperative arrhythmia,high preoperative platelet count,high preoperative D-dimer concentration,intraop-erative hypotension,and administration of intraoperative norepinephrine are risk factors for new DVT within 6 hours after general anesthesia in AICU patients.

BACKGROUND:Bone mineral density is the clinical gold standard for determining bone strength,but bone mineral density is less sensitive to changes in bone mass,with large changes in bone mineral density only occurring when bone mass is significantly reduced,so bone mineral density has limited ability to predict changes in bone strength and fracture risk. OBJECTIVE:A model of the normal and osteoporotic hip joint was developed to analyze the stresses and deformation in the hip of normal and osteoporotic patients under single-leg standing conditions. METHODS:A healthy adult female volunteer at the age of 36 years was selected as the study subject.The CT data of the hip joint of this volunteer were obtained and saved in DICOM format.The hip joint model was reconstructed in three dimensions,and the material properties were assigned by the gray value assignment method to obtain the normal and osteoporotic hip joint models according to the empirical formula.The same boundary conditions and loads were set to simulate the stresses and deformation in the normal and osteoporotic hip joints in the single-leg standing position. RESULTS AND CONCLUSION:(1)In the finite element model of the normal and osteoporotic hip,the stress distribution was more concentrated in the medial region of the femoral neck.(2)In the hip bone,the stress distribution was mainly concentrated in the upper part of the acetabulum.(3)The stress peaks in the medial femoral neck and upper acetabulum were larger in the normal hip model than in the osteoporotic hip model,probably due to the reduced bone strength of the osteoporotic bone.(4)The peak Von Mises of both normal and osteoporotic hip models were concentrated on the medial femoral neck,and the peak Von Mises of the hip bone was smaller,indicating that the overall effect of osteoporosis on hip bone stresses was relatively small.(5)In terms of deformation in the single-leg standing position,the maximum deformation in the normal hip model was located at the acetabulum and femoral head,and the maximum deformation was located at the upper part of the greater trochanter of the femur.(6)It is suggested that the finite element analysis method to model the values of parameters related to bone tissue in osteoporosis may improve clinical prediction of bone strength changes and fracture risk.It is explained from the biomechanical view that the intertrochanteric femur and femoral neck are good sites for osteoporotic hip fractures.